The active metabolites of the mitomycins and pyrrolizidine alkaloids are related in that both groups possess acylated vinylogous carbinolamine moieties as an essential pharmacophoric group. The significant difference between these two groups of naturally-occurring tumor inhibitors lies in the chemical reactivity of the active metabolites and the associated toxicity. Effective control of the chemical reactivity of the acylated vinylogous carbinolamine appears to be a significant determinant for antineoplastic activity and toxicity. The objectives of the proposed research are to prepare a number of pyrroles, pyrrolizines, and other related heterocycles which possess the bis(acyloxymethyl) functions for antineoplastic evaluation. QSAR methods will be used to evaluate the data. Structure activity studies are proposed in order to determine the significance of chemical reactivity, solubility, intercalative-binding to DNA, and charge-transfer catalysts as they affect antineoplastic activity (particularly against the more intractable solid tumors) and toxicity. The study also proposes to synthesize carbon-14 labeled compounds for metabolism studies and for studies on covalent drug binding to biomacromolecules.